SIR: In “Prodromal Symptoms in Panic Disorder With Agoraphobia” (1), Giovanni A. Fava, M.D., and associates reported that of 20 patients suffering from panic disorder with agoraphobia, 18 had experienced agoraphobic avoidance, generalized anxiety, and/or hypochondriacal fears and beliefs during the 6 months before the first panic attack. Normal control subjects reported significantly fewer of these phenomena in the 6 months before they had an identical interview. Dr. Fava and his colleagues concluded from these data that agoraphobic symptoms are more primary than panic attacks in panic disorder with agoraphobia-a reversal of the causal sequence assumed in DSM-III-R. Imipramine’s effects in agoraphobic patients originally suggested that panic attacks were the primary disturbance in most such patients and that anticipatory anxiety and agoraphobic avoidance followed as reactions to the initially unexpected anxiety episodes (2). As noted by Dr. Fava and associates, several subsequent investigations generally affirmed this phenomenological sequence. Limiting the usefulness of the data from Dr. Fava’s group are three important methodological issues. First, it is unclear whether the patients and control subjects were interviewed about prior symptoms by persons blind to diagnosis, so as to avoid investigator bias. Second, the degree of agoraphobia, generalized anxiety, or hypochondria found in the patient group before panic onset was not specified. While it appears that these levels exceeded some threshold and therefore differed from what was found in the control subjects, the investigators did not specify whether the patients suffered clinically severe agoraphobic symptoms before their panics began or whether these developed only after the onset of panic. Also, Dr. Fava and colleagues cited Weissman and Merikangas’s finding (3) that a sizable percentage of agoraphobic patients in epidemiological samples did not have panic attacks, but without specifying that many of them had limited-symptom (partial panic) attacks. This does not appear to have been investigated by Dr. Fava’s group.